Ramipril
Symptoms of arterial hypotension. In patients with uncomplicated arterial hypertension, symptoms of arterial hypotension are rare. In patients with hypertension taking ramipril, the likelihood of developing arterial hypotension increases with decreasing BCC (for example, as a result of treatment with diuretics,restriction of dietary intake, dialysis, diarrhea, or vomiting), as well as severe forms of renin-dependent hypertension. Symptoms of arterial hypotension were observed in patients with heart failure, regardless of whether it is combined with renal insufficiency. This is most often observed in patients with more severe heart failure who are forced to take high doses of "loop" diuretics who have hyponatremia or functional renal failure. Patients with an increased risk of hypotension need close monitoring in the initial period of treatment and in the selection of a dose. This also applies to patients with ischemic heart disease or cerebrovascular disease, in whom a significant drop in blood pressure can lead to myocardial infarction or cerebrovascular accident. In the case of arterial hypotension, the patient should be placed on his back, legs raised and, if necessary, an intravenous infusion of sodium chloride solution. Transient hypotensive reaction is not a contraindication for the subsequent administration of the drug.In some patients with heart failure who have normal or low blood pressure, ramipril may cause an additional decrease in systolic blood pressure. This effect can be foreseen, therefore it is usually not a basis for discontinuing treatment. If hypotension is symptomatic, it may be necessary to reduce the dose or stop treatment.
Aortic and mitral stenosis / hypertrophic cardiomyopathy. Like other ACE inhibitors, ramipril requires caution in appointing patients with aortic stenosis or difficulty in ejection from the left ventricle (for example, in aortic stenosis or hypertrophic cardiomyopathy). In some cases, the hemodynamic picture may make it unacceptable to take a fixed combination of ramipril and hydrochlorothiazide.
Women taking the drug during pregnancy (beginning with the second trimester), it is necessary to undergo ultrasound to check the condition of the kidneys and the skull of the fetus.
Primary aldosteronism (Conn's disease). The use of fixed combinations of ramipril and hydrochlorothiazide is contraindicated,since patients with primary aldosteronism are not sensitive to antihypertensive agents, the action of which is based on suppression of the renin-angiotensin system.
Impaired renal function. In patients with heart failure at the beginning of treatment with ACE inhibitors, impaired renal function may be observed. In such situations, cases of acute renal failure, usually transient, are described.
In some patients with narrowing of both renal arteries or with stenosis of the artery of a single kidney, ACE inhibitors increase the level of urea and creatinine in the blood; usually these changes occur after discontinuation of medication.
The likelihood of this is especially high in renal failure. In the presence of renovascular hypertension, the risk of severe arterial hypotension and renal failure is high. In such patients, treatment should be started under close medical supervision with small doses, which must be accurately matched. Because diuretics can contribute to the clinical dynamics described above, during the first weeks of treatment with ramipril, their intake should be discontinued and the kidney function needs careful monitoring.
In some patients with arterial hypertension without an obvious disease of the kidneys of the kidneys, taking ramipril, especially against the background of diuretics, causes an increase in the level of urea and creatinine in the blood; these changes, as a rule, are insignificant and transitory.
The probability of their occurrence is higher in patients already suffering from impaired renal function. In such cases, it may be necessary to reduce the dose and / or stop taking the diuretic and / or ramipril.
Condition after kidney transplantation. In connection with the lack of experience with the use of ramipril in patients who have recently undergone kidney transplantation, ramipril it is not recommended to take such patients.
Hypersensitivity / angioedema. Angioedema, facial edema, extremities, lips, tongue, vocal cords and / or larynx rarely develops in patients receiving ACE inhibitors, incl. ramipril. During treatment, angioedema may develop at any time. In this case, the taking of ramipril should be stopped immediately, the appropriate treatment should be carried out and the patient should be monitored; Before releasing the patient, you should make sure that all the symptoms of the edema are eliminated.Even in cases where edema is limited to the tongue and signs of breathing are not present, patients may need long-term follow-up, since treatment with angstamines and corticosteroids may not be sufficient. In rare cases death of patients due to angioedema of the larynx or tongue is documented.
If swelling spreads to the tongue, vocal cords, or larynx, it is very likely that the airway is blocked, especially in patients who have previously undergone surgery on the respiratory system. In such cases it is necessary to take emergency therapy. It can include the administration of epinephrine (adrenaline) and / or maintenance of airway patency. The patient should be under careful medical supervision until the symptoms disappear completely and persistently.
Patients who have a history of angioedema, not associated with the administration of ACE inhibitors, may be at increased risk of developing angioedema in response to an ACE inhibitor.
Anaphylactoid reactions in patients on hemodialysis. There are reports of anaphylactoid reactions in patients on hemodialysis using membranes with high hydraulic permeability (e.g. AN69) while the use of ACE inhibitors. In such cases, another type of membrane or other antihypertensive medication should be considered.
Anaphylactoid reactions in the apheresis of low-density lipoproteins. In rare cases, in patients taking an ACE inhibitor against apheresis low density lipoprotein with the help of dextran sulfate, life-threatening anaphylactoid reactions develop. Such reactions can be avoided if temporarily refraining from taking an ACE inhibitor before each apheresis procedure.
Desensitization. Patients taking ACE inhibitors on the background of desensitizing therapy (eg intoxication with poison Hymenoptera), developing long-term anaphylactoid reactions. If such patients refrained from taking ACE inhibitors for the time of desensitization, no reactions were observed, but a random injection of ACE provoked an anaphylactoid reaction.
Liver failure. With the administration of ACE inhibitors, the development of a rare syndrome that starts with cholestatic jaundice or hepatitis is associated with transient hepatic necrosis, sometimes fatal. The mechanism of development of this syndrome is not clear. If patients taking ramipril, jaundice develops or the activity of liver enzymes increases significantly, the drug must be canceled, leaving the patient under the supervision of a doctor until the symptoms disappear.
Neutropenia / agranulocytosis. It has been reported that patients taking ACE inhibitors may develop neutropenia / agranulocytosis, thrombocytopenia and anemia. With normal kidney function and in the absence of complications, neutropenia develops rarely. Neutropenia and agranulocytosis are reversible and pass after discontinuation of the ACE inhibitor. Caution should be exercised when appointing ramipril to patients suffering from connective tissue diseases with vascular manifestations undergoing treatment with antidepressants taking allopurinol or procainamide, as well as a combination of these factors, especially against a background of impaired renal function.Some of these patients develop severe infections that are not always amenable to intensive antibiotic therapy. If the treatment of such patients is used ramipril, it is recommended to periodically check the number of white blood cells, and patients should be warned about the need to report any signs of infection.
Race affiliation. ACE inhibitors often cause the development of angioedema in patients of the Negroid race as compared to patients of other race.
Like other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black patients than in other races, possibly due to a higher incidence of low renin in a population of black patients suffering from hypertension.
Cough. It was reported that the administration of ACE inhibitors may be accompanied by a cough. It is characteristic that the cough is dry and persistent; it passes after the drug is discontinued. The fact that the cough is caused by the intake of an ACE inhibitor should be considered as a differential diagnostic feature.
Surgery / general anesthesia.
In patients undergoing surgery or general anesthesia with drugs that reduce blood pressure, ramipril can block the increase in the formation of angiotensin II under the influence of compensatory release of renin. If it is assumed that arterial hypotension develops by this mechanism, it can be corrected by an increase in BCC.
Hyperkalemia. In some patients taking ACE inhibitors, including ramipril, there is an increase in potassium in the serum. The group of risk of hyperkalemia include patients suffering from renal insufficiency or diabetes, taking potassium-sparing diuretics or kalisodergaszczye solezameniteli, as well as those patients who are taking other drugs that increase serum potassium (eg heparin). If the administration of the above drugs against the background of treatment with an ACE inhibitor is recognized as necessary, regular monitoring of serum potassium levels is recommended.
Patients with diabetes mellitus. Diabetic patients taking hypoglycemic agents for oral or insulin, you must carefully control the level of blood sugar during the first month of treatment with an ACE inhibitor.
Lithium. It is usually not recommended to combine lithium and ramipril (see "Interaction").
Potassium-containing food additives, potassium-sparing diuretics or potassium-containing salt substitutes. Although serum potassium levels in clinical studies of ACE inhibitors usually remained within normal limits, some patients still developed hyperkalemia.
The risk of developing hyperkalemia is associated with a number of factors, including renal insufficiency, diabetes mellitus, and simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene or amiloride), as well as potassium-containing food additives or salt substitutes. The use of potassium-containing food additives, potassium-sparing diuretics or potassium-containing substitutes can lead to a significant increase in potassium levels in the serum, especially in patients with impaired renal function.
During the reception of ramipril on the background of potassium-releasing diuretics, hypokalemia caused by their intake may be weakened.
Hydrochlorothiazide
Impaired renal function. In patients with kidney disease, thiazides can cause azotemia.Their use against a background of impaired renal function can lead to cumulative effects. If kidney failure improves, characterized by an increase in non-protein nitrogen, the need for therapy should be carefully assessed and the possibility of stopping diuretics should be considered.
Violation of the function of the liver. Patients with a violation or progressive impairment of liver function, thiazides should be administered with caution, since even minor fluctuations in the water-electrolyte balance can cause hepatic coma.
Metabolic and endocrine effects. Thiazide therapy can reduce glucose tolerance. With diabetes, it may be necessary to choose a dose of insulin or oral hypoglycemic agents. Thiazide therapy can cause a manifestation of latent diabetes mellitus. With therapy, thiazide diuretics are associated with an increase in cholesterol and triglyceride levels. In some patients receiving thiazide diuretics, there may be an increase in the level of uric acid or the manifestation of gout.
Gout. In some patients, thiazide therapy may increase the level of uric acid and / or cause gout.but ramipril can increase the excretion of uric acid, thereby weakening the degree of increase in the level of uric acid under the influence of hydrochlorothiazide.
Violations of the water-electrolyte balance. Any patient receiving treatment with diuretics should periodically determine the content of electrolytes in the blood serum.
Thiazides, including hydrochlorothiazide, can cause disturbance of water-electrolyte balance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Precipitation of water or electrolyte balance disturbance is dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, myalgia or muscle spasms, muscle fatigue, arterial hypotension, oliguria, tachycardia and such gastrointestinal disorders as nausea and vomiting.
Although the use of thiazide diuretics and may lead to the development of hypokalemia, with simultaneous administration of ramipril, a decrease in the degree of hypokalemia caused by diuretics is possible. The likelihood of hypokalemia is greatest in cirrhosis, in patients with elevated diuresis, inadequate oral administration of electrolytes,as well as against the background of corticosteroids and ACTH.
In hot weather, it is possible to develop hyponatremia in patients with peripheral edema. The lack of chlorides is usually minor and does not need treatment. Thiazides can reduce the excretion of calcium ions in the urine, resulting in a slight periodic increase in the level of calcium in the blood, even in the absence of obvious violations of calcium metabolism. Explicit hypercalcemia may indicate latent hyperparathyroidism. The administration of thiazides should be discontinued until the results of the parathyroid gland function are obtained. It has been shown that thiazides increase the renal excretion of magnesium, which can lead to a decrease in the level of magnesium in the blood.
Neutropenia / agranulocytosis.
The combination of fixed doses of ramipril and hydrochlorothiazide should be discontinued if neutropenia occurs or is suspected (neutrophil count <1000 / mm3).
Anti-doping tests. Hydrochlorothiazide, which is part of this medication, can give a positive reaction in the anti-doping control.
Other. Regardless of the history of allergies or bronchial asthma,in patients may develop sensitivity reactions. The possibility of exacerbation of systemic lupus erythematosus was reported.
Influence on the ability to drive a car or perform work that requires an increased speed of physical and mental reactions.
Care must be taken when driving a vehicle and working with mechanisms that require special attention.
The combination has a weak or moderate effect on the ability to drive and work with machinery. Due to differences in individual reactions, some patients may be impaired ability to drive, work with mechanisms, and perform other types of work that require increased attention. This is especially pronounced at the start of treatment and / or after an increase in dosage.